Tetrahydrofuran → Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfanyl)pyrimidine-5-carboxylate

HRID 917586Notes

Reaction equation

HRID 917586 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7](Cl)[C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][N:4]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH2:24][NH2:25])[CH:19]=[CH:20][C:21]=1[O:22][CH3:23].C(N(CC)CC)C.O1CCCC1>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[CH3:1][S:2][C:3]1[N:8]=[C:7]([NH:25][CH2:24][C:18]2[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:16]([Cl:15])[CH:17]=2)[C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 7380383-Chloro-4-methoxybenzylamine

Product 1

HCID 22025927Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfanyl)pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 311Citric AcidSolvent

Procedure

(1)-a) A mixture of 2-methylthio-4-chloro-5-ethoxycarbonylpyrimidine 1.0 g, (3-chloro-4-methoxyphenyl)methylamine 0.81 g, triethylamine 0.66 ml and tetrahydrofuran 12 ml is stirred for 4 hours at room temperature. The reaction mixture is diluted with an aqueous 10% citric acid solution and the mixture is extracted twice with ethyl acetate. The combined organic layer is washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is purified by silica gel chromatography (solvent; hexane:ethyl acetate=5:1) and concentrated in vacuo to give a colorless oil. The oil is left overnight at room temperature to give 2-methylthio-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine as crystals, 1.58 g. mp 82-83° C.

Workup

  1. extractionthe mixture is extracted twice with ethyl acetate
  2. washThe combined organic layer is washed with water
  3. dry with materialan aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel chromatography (solvent; hexane:ethyl acetate=5:1)
  6. concentrationconcentrated in vacuo
  7. customto give a colorless oil
  8. waitThe oil is left overnight at room temperature

Sources & evidence

ORD record
ord-675beb9ad18646adab52126ab74e59d8
Source dataset
uspto-grants-2007_09
Patent number
US07273868B2

Reaction notes

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